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Metachromatic leukodystrophy (MLD) is Alzheimer’s on speed. Children born with the most common form of the disease will die by age five, due to atrophy of brain tissue. The incidence in the general population is estimated to be 1 in 40,000 to 160,000 births.
Unlike Alzheimer’s, MLD has a known genetic cause. It has an autosomal recessive inheritance pattern, which means a child must inherit a defective, recessive gene from each of two carrier parents to be symptomatic. That suggests the frequency of carriers in the population is 1 in 200 to 1 in 400. But for couples who are both carriers, the odds of a child with MLD are 1 in 4.
Post-natal testing does not work on MLD. The enzyme test that reveals the disease has a 7-15 percent false positive rate due to other, less severe conditions affecting the same body chemistry. Unless a specific genetic test is done on the parents or the pre-natal fetus, the first time most affected couples will know is when their child exhibits unmistakable symptoms. By that point, the disease in untreatable and irreversible. And there are 1 in 4 odds that any future child of theirs will die the same way (see illustration).
There is hope. This is a case where post-natal gene therapy seems to be effective. An MIT Technology Review article describes a technique to modify extracted stem cells with a corrected gene and reinsert them in the child’s body, reversing the disease. As far as can be determined with a small sample size over a few years, it appear to be safe and effective: that is, a genuine cure. Amazingly, the whole development in an Italian clinic has been supported by national telethons and philanthropy. Huzzah for the Italians!
The MIT article raises several issues, but without pause or analysis. I extract two passages to frame the dilemmas:
…treatments have been purchased by British drug giant GlaxoSmithKline, which is pursuing commercialization of the therapies. By adding correct DNA code to cells, gene therapy has the potential to erase devastating illnesses with a one-time treatment.
On one hand, a GSK pickup means the therapy will no longer live on charity. But what will it cost? Remember, this is a cure, offering no recurring revenue stream from afflicted patients. The costs of conclusive clinical trials and manufacturing must be amortized across the limited number of victims, one time each. And, of course, who pays? And if not the individuals concerned, what onus is there on others to pay for a stranger’s care?
Mind you, this is a cure for the child’s lifetime only. It does not modify the germ cells. A child with MLD who survives to reproduce — which will now happen at far greater frequency — will pass a copy of the bad gene to every offspring. Good for the individual, bad for the human gene pool, creating further potential costs down the road. Some believe that tampering with the germline is ethically problematic, but this case demonstrates the down-side of not doing so. Is it counterproductive — is it ethical — to save the current suffering at the cost of more in the future?
…[the mother] also disagreed with the Italians’ advice to get a prenatal genetic test during her two subsequent pregnancies to learn in advance if the fetuses would be affected, as she wouldn’t consider abortion. She had four more children, three of them in 2014 when she delivered natural fraternal triplets (there are one-in-8,100 odds of that). One of them, Cecilia, also had inherited the MLD genes. The Italians accepted the second baby into the study and treated her…
The American couple in question now have eight children, three (one deceased) with MLD. They live on a single house remodeler’s income. They are a charity case. Luckily, the Italians stepped in, not just once but twice.
What are the chances such a family would be able to afford GSK’s cure in the future? Should they be subsidized if they continue to procreate, knowing there’s a 25% chance that their children will need care they cannot afford? Should society support this? Can an obligation be created to test and yes — abort — once the hazard is known? What can we say about the ethics of such parents, or, on the other hand, a societal decision to turn its back on children born in such a situation?
We are going to see a spate of novel and effective gene therapies in the near future, due to advances such as CRISPR, but having cures is not going to end the dilemmas of treatment.Published in